Tooth development is a highly reguated process orchestrated by a number of genes that encode growth factors, transcription factors and extracellular matrix proteins. Molecular mechanisms underlying the noral and abnormal tooth development is not well characterized. We have initiated studies that focus on the candidate genes for the common tooth disorders such as dentinogenesis imperfecta (DGI), dentin dysplasia and osteognensis imperfcta as well as growth factor genes involved in tooth mineralization.Dentin sialophosphoprotein (DSPP) gene is a prime candidate for DGI-II. It encodes a non-collagenous protein that is specifically expressed in odontoblasts and ameloblasts during tooth development. We have clonedand characterized the murine DSPP homolog and targeted its locus mouse embryonic stem cells in order to generate a gene knockout model for DGI-II. Secondly, using the DSPP promoter we targeted expression of candidate genes in developing tooth to delineate their specific roles in tooth development. Studies are underway to characterize the - Dentinogenesis, molecular genetics, gene knockout, growth factors, extracellular matrix, mineralization